We are undertaking an imaging initiative to build a hyperlens nanoscope, using newly advanced meta-material hyperlens technology, to achieve superior temporal and spatial resolution and to investigate membrane dynamics during brain synaptic transmission and cellular endocytosis/exocytosis in general. The hyperlens consists of specially designed and micro-fabricated structure elements that can magnify near-field images at sub-diffraction-limited spatial resolution and project the high resolution image at far-field in real time (Yao, et al, 2008, Science, 321:930;Liu, et. al, 2007, Science, 315:1686;Fang, et. al, 2005, Science, 308:534-7). This form of optical nanoscope possesses some unique advantages of both real-time optical imaging (at video rate) and nano-metric spatial resolution, in comparison with other imaging techniques such as EM, STED (Hell, 2007, Science, 316: 1153-8), and STORM/PALM (Huang, et al., 2008, Science, 319:810-813;Bates, et. al, 2007, Science 317, 1749-53;Hess, et al, 2007, PNAS 104, 17370-5;Betzig, et. al, 2006, Science 313:1642). Hyperlens-related technology is under rapid development led by the groups of Prof. Cheng Sun (extramural collaborator now at Northwestern University) and Prof. X. Zhang (UC Berkeley). After winning an equipment grant from the trans-NIH imaging initiative, we have been developing our imaging setup at NIH and are working to resolve modeling and nano-manufacturing issues toward improved hyperlens design and construction. In this project year, we have also investigated bovine chromaffin cells (fixed or live, or transfected with various fluorescent protein constructs) as a vesicular trafficking model system, by leveraging our related experience on multimodal instrumentation around atomic force microscopy (AFM) and various optical microscopy platforms. We are still working toward breakthrough investigations of sub-cellular membrane dynamics for both fundamental biology and medicine.